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Combined Effect Of Lead And Cadmium On DMT1 Expression In Central Nervous System Of Budding Rat

Posted on:2009-09-11Degree:MasterType:Thesis
Country:ChinaCandidate:C W GuFull Text:PDF
GTID:2120360248454564Subject:Genetics
Abstract/Summary:PDF Full Text Request
Background: Both Pb and Cd are ubiquitous pollutants in the environment. The central nervous system(CNS)in development phase is more vulnerable to deleterious effects of lead and cadmium than other tissues. Divalent metal transporter 1(DMT1)is the first mammalian transmembrane iron transporter to be identified. And it is mainly involved in transport of nonheme iron. Other divalent metals, such as Mg2+, Co2+, Cd2+, Zn2+, Ni2+ and Pb2+, can also be transported competively through DMT1. The effect of iron on DMT1 expression has been clear. Dietary iron deficiency can induce DMT1 mRNA expression and protein synthesis in many tissues such as brain and duodenum, and high dietary iron load appears the opposite effect. However, the interactions between DMT1 expression and other divalent metals during development phase are less well studied. Iron deficiency can reinforce lead and cadmium toxicity. Both tissue lead and cadmium levels rise during the iron storage deficiency. Both lead and cadmium toxicity can cause anemia, the reasons for which are poorly understood besides lead can inhibit some enzymes related to synthesis of hemoglobin, and on which needs further research.Objective: To provide some scientific basis for the revealment of lead and cadmium neurotoxin mechanism, the present study was undertaken to observe the effects of lead acetate and cadmium chloride on DMT1 mRNA expression and protein synthesis in cerebellum, cortex and hippocampus of budding rats.Material and Method: 24 healthy male Sprague-Dawley 30-day-old rats were randomly divided into 4 groups with 6 rats in each: distilled water for negative control group, 20mg/(kg·d)lead acetate for Single Lead group, 2mg/(kg·d)cadmium chloride for Single Cadmium group, both 20mg/ (kg·d)lead and 2mg/(kg·d)cadmium for Association Group. Lead and/or cadmium solution or water was given to rats through gastric perfusion everyday for 6 weeks respectively. The 6 rats of each group were executed by decapitation, and then the blood was collected to measure the Lead and cadmium concentrations by atomic absorption spectrophoto-metry. The cerebellum, cortex and hippocampus tissue were separated from each rat. The expression of DMT1 mRNA was observed by RT-PCR technique. The DMT1 protein synthesis was detected by Western Blotting method. All amount of data was compared with β-actin. The statistical calculations were performed using SPSS13.0Result: Blood lead level of single-lead group and blood cadmium level of Single-Cadmium group are much higher than Control group (P<0.01). There is no difference of blood lead level between Single-Cadmium group and Control group. But significant difference of blood cadmium level was observed between Single-Lead group and Control group. Moreover, markedly differences of blood lead and cadmium levels between Lead-Cadmium Association group and Control group were detected (P<0.05). With the perfusion of lead and cadmium, DMT1 mRNA expression did not change, but significant difference of DMT1 protein synthesis between all 4 groups was observed. Lead and cadmium performed the positive effects on DMT1 expression in rat brain.Conclusion: Lead and cadmium exposure can result in elevated blood lead and cadmium levels. Lead exposure results in significant increase of cadmium absorption, but cadmium exposure has no effect on lead dietary uptake. Both lead and cadmium can induce DMT1 protein synthesis without up-regulation of DMT1 mRNA expression in central nervous system, and lead and cadmium has synergism effects on DMT1 protein synthesis. which is, maybe, one of their neurotoxic mechanisms in central nerve system.
Keywords/Search Tags:Lead, cadmium, neurotoxicity, divalent metal transporter 1, synergism effect
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